Infecciones helmínticas pulmonares

Introduction

The term “parasitism” denotes a relationship between2 living organisms that has harmful consequences for 1of the 2 (the host) and is beneficial to the other (theparasite). Although, in theory, the term “parasite”covers all organisms capable of causing damage toothers, in medicine it has traditionally been usedexclusively to refer to the protozoa, helminths, andarthropods that live temporarily or permanently inhumans.1 While a parasitic infection may give rise toclinical manifestations (parasitic diseases), it can alsobe asymptomatic.1 With certain exceptions (chieflysevere amebiasis and malaria2), most of the parasitesthat affect the lungs are helminths, that is, invertebrateorganisms resembling worms (vermes).

In this article we will review the whole range ofrespiratory diseases caused by these parasites in humans,providing an update on several topics dealt with inARCHIVOS DE BRONCONEUMOLOGÍA by Cremades3 in1998. We will begin with a brief overview of the maingenera and species involved, followed by a descriptionof the point in the life cycle of each parasite whencontact with the respiratory apparatus takes place. Thesecond part of the article is a review of the principalepidemiological characteristics, with particular emphasison the geographical distribution of these diseases. Thisis followed by a description of the mechanisms of lunginjury (the parasite’s aggression and the host’s defense)and of the clinical signs and symptoms produced. Thefinal 2 sections cover diagnostic techniques and possibletreatments.

Causal Agents

The chief human helminth infections are caused byvarious species of cestodes, trematodes, and nematodes.The forms of cestodiasis that affect the lungs are causedexclusively by larvae and never by adult worms (forexample, Taenia saginata, Taenia solium, Diphyllo-bothrium latum, Hymenolepis species, and Dipylidiumcaninum). The main form of cestodiasis that affects thelung is hydatidosis or echinococcosis (caused byEchinococcus granulosus),4 while the lungs are onlyrarely affected by cysticerci (a larval form of T solium)5-7

or other species of Echinococcus (Echinococcusmultilocularis, Echinococcus vogeli, and Echinococcusoligarthrus).4 The 2 genera of trematodes that can damagethe lungs are Schistosoma and Paragonimus. Whilevarious species of the former can cause schistosomiasis,the disease is most often caused by Schistosoma mansoni,Schistosoma haematobium, and Schistosoma japonicum.8

Schistosomiasis can affect the lung in 2 ways: Katayamasyndrome during the acute phase, and embolization ofeggs to the pulmonary arterioles during the chronicphase.8 Paragonimiasis is caused by infection with variousspecies of Paragonimus, primarily Paragonimuswestermani.9,10 Finally, the following types ofnematodiasis can affect the lung: a) disease caused bycertain intestinal helminths that inhabit the lung at somepoint in their life cycle, such as Ascaris species,hookworms (Ancylostoma duodenale and Necatoramericanus), and Strongyloides species11,12; b) someforms of lymphatic filariasis (caused by Wuchereriabancrofti, Brugia malayi, and Brugia timori)13 anddirofilariasis (caused by Dirofilaria immitis)14; and c)tissue invading nematodiasis, such as toxocariasis (causedby Toxocara canis and Toxocara cati)15 and trichinosis(caused by various species of Trichinella).16

Fundamental Biological Characteristics

These helminths enter the host organism by 3different routes (Figure). E granulosus, P westermani,

Correspondence: Prof. J.L. Pérez-Arellano.Departamento de Ciencias Médicas y Quirúrgicas. Centro de Ciencias de la Salud.Universidad de Las Palmas de Gran Canaria.35080 Las Palmas de Gran Canaria. Las Palmas. España.E-mail: [email protected]

Manuscript received February 11, 2005. Accepted for publication March 1, 2005.

Arch Bronconeumol. 2006;42(2):81-91 81

REVIEW ARTICLE

Helminths and the Respiratory System

J.L. Pérez-Arellano,a,b M.A. Andrade,c J. López-Abán,c C. Carranza,b and A. Muroc

aUnidad de Enfermedades Infecciosas y Medicina Tropical, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain.bDepartamento de Ciencias Médicas y Quirúrgicas, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain.cLaboratorio de Inmunología Parasitaria y Molecular, CISET, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.

Ascaris lumbricoides, A duodenale, and helminths ofthe Toxocara and Trichinella species enter when thehost organism ingests food or water containing infectiveforms of the parasite. Schistosoma species,Strongyloides stercoralis, and hookworm penetrate thebody through the skin. The filariae are transmitted byvarious arthropod vectors.

E granulosus has an indirect life cycle. The canids andsome felids are the hosts of the adult forms of thiscestode, and the larvae (metacestodes) are found in anumber of intermediate hosts, mainly ungulates androdents.4,17 Humans become accidental intermediate hostswhen they ingest helminth eggs, either directly from thedefinitive host or in water or vegetables contaminatedwith the excretions of the definitive hosts. Once ingested,eggs hatch in the small intestine and release oncospheresthat burrow into the intestinal wall. These oncospherestravel through the bloodstream to the liver, where most ofthem remain. Some, however, travel through the venoussystem to the lung and may even pass through thepulmonary filter and reach other organs by way of thesystemic circulation. Occasionally, cases have beenreported in which oncospheres reached the lung from theintestinal tract through the lymph system (bypassing thepulmonary filter) or from the bronchial tree.17 When theyreach the target organs, the oncospheres that have notbeen destroyed by the immune system form hydatid cyststhat gradually grow in size as protoscolices and broodcapsules are formed in their interior.17

The different species of Schistosoma have an indirectcycle involving several species of freshwater snail (of the

genera Biomphalaria, Bulinus, and Oncomelania), whichfunction as specific intermediate hosts. Several phases ofthe schistosome’s life cycle take place inside these hostsbefore cercariae are released into water.8 The cercariaeare able to penetrate intact skin, and once inside thehost’s body they shed their tails to becomeschistosomula. These larvae migrate through the venousbloodstream to the pulmonary circulatory system andcross through it. Initially they invade the left chambers ofthe heart and later the mesenteric (S mansoni) or vesical(S haematobium) veins, where sexual differentiationtakes place. The males and females are coupled in pairs,and eggs are released after fertilization has taken place.These eggs travel in both anterograde and retrogradedirections, giving rise to the lesions characteristic of thisdisease (granulomas). In the course of this “chronic”phase, the lung is damaged when branches of thepulmonary arteries become embolized by eggs.

The cycle of the trematodes of the genus Paragonimus,which is also indirect but more complex than that of theschistosomes, involves 2 types of intermediate hosts:water snails (such as Aroapyrgus species, in which a cyclesimilar to that of the schistosomes takes place); andcrustaceans (in which the cercariae become meta-cercariae).9 Humans become infected when they eat rawor undercooked crustaceans (especially crabs) that containmetacercariae. These metacercariae excyst in the intestinaltract. The larvae then migrate through the intestinal wallinto the peritoneal cavity and subsequently cross thediaphragm into the pleural space. The immature wormsthen burrow into the pulmonary tissue, where theymature, giving rise to cysts containing bloody purulentfluid enclosed in a fibrous capsule. When the eggs arefinally released they are expelled through the airway.9

The intestinal helminths mentioned above (Ascarisspecies, A duodenale, N americanus, and Strongyloidesspecies) affect the lung when they migrate through thebronchial tree. Infection with Ascaris species,18 andsometimes with A duodenale, is caused by theconsumption of food infected with embryonated eggs ofone of these nematodes. The eggs hatch in the intestinaltract, releasing larvae that penetrate the intestinal wall andare then carried by the venous bloodstream to the liver(where they cause no damage) and from there continue onthrough the right heart chambers to the pulmonarycapillary bed. Eventually they cross the alveolocapillarymembrane and migrate up the airway through thebronchioles, the bronchi, and the trachea until they reachthe pharynx. At this point they are swallowed and returnto the small intestine, the final home of the mature worm.Hookworm infection19 and S stercoralis infection20 usuallyfollow a different cycle. The filariform larvae (third stage)enter the organism through the skin as a result of contactbetween bare feet and the ground. They migrate via thevenous bloodstream to the branches of the pulmonaryartery, and then follow a life cycle similar to that of theother intestinal helminths. An important differencebetween S stercoralis and the other helminths is that it canreinfect the host from the intestine.

PÉREZ-ARELLANO JL ET AL. HELMINTHS AND THE RESPIRATORY SYSTEM

82 Arch Bronconeumol. 2006;42(2):81-91

Figure. Helminth entry routes.

Schistosoma speciesHookwormStrongyloides species

Echinococcus granulosusParagonimus westermaniAscaris lumbricoidesAncylostoma duodenaleToxocara speciesTrichinella species

Wuchereria bancroftiBrugia malayiBrugia timoriDirofilaria inmitis

The filariases are the most common type of bloodnematodiasis. Pulmonary involvement follows 2different patterns: on the one hand, lymphaticfilariasis—caused by W bancrofti and Brugia speciesand transmitted by various hematophage insects in theDiptera order—causes pulmonary lesions through therelease of microfilariae that become trapped in thepulmonary vascular bed13; on the other hand, in patientswith D immitis infection, lung injury is caused byembolization of larvae to the pulmonary vasculature.14,21

Toxocariasis occurs when the host ingestsembryonated eggs present in soil contaminated withstools from infected dogs and cats. Logically, thisdisease is more prevalent in young infants. The eggshatch in the small intestine, releasing second-stagelarvae that penetrate the intestinal wall, enter thebloodstream, and travel to various structures, such as theliver, the lungs, the central nervous system, and theocular globe.22

Infection with different species of Trichinella iscaused by the consumption of raw or undercooked meatfrom infected pigs or boar.16 Excystation takes place inthe intestinal tract. This is followed by sexualdevelopment, the fertilization of the females, and therelease of first-stage larvae. These larvae enterlymphatic tissue and vessels and migrate to striatedskeletal muscle, including the diaphragm and otherrespiratory muscles. The larvae then burrow into thesemuscles, where they grow and encyst.

Table 1 summarizes the main differences between thevarious helminths that affect the respiratory system.

Epidemiology

The distribution of E granulosus infection iscosmopolitan, and prevalence varies considerably fromcountry to country and even within each country.23,24 Themost important hyperendemic areas are the Mediterranean



TABLE 1Causative Agents and the Basic Characteristics of the Life Cycle of Helminths That Affect the Respiratory System

Genus Species Type of Cycle Definitive Intermediate Method of ContagionHost(s) Host(s)

Echinococcus E granulosus Indirect Canids Ungulates, humans Ingestion of eggs.Contact with dogsConsumption of water

or food

Schistosoma S mansoni Indirect Humans Fresh water snails Transdermal penetrationS haematobium by cercariaeS japonicum*

S intercalatumS mekongi

Paragonimus P westermani Indirect Humans, other Fresh water snails (1st). Consumption of raw ormammals Crustaceans (2nd) undercooked crustaceans

Ascaris A lumbricoides Direct Humans Ingestion of eggsin water or food

Ancylostoma A duodenale Direct Humans Transdermal penetrationby larvae

Ingestion of eggsin water or food

Necator N americanus Direct Humans Transdermal penetrationby larvae

Strongyloides S stercoralis Direct Humans Transdermal penetrationby larvae

S fuellerborni Autoinfection

Wuchereria W bancrofti Indirect Humans Hematophage Diptera (Culex Introduction of larvaeBrugia B malayi species, Aedes species, by insect bite

B timori Anopheles species)

Dirofilaria D immitis Canids

Toxocara T canis Direct Dogs Ingestion of eggsT cati Cats present in the soil

Trichinella T spiralis Autoheteroxenous Mammals, Ingestion of raw orT nativa humans undercooked meat fromT britovi infested animalsT murrelliT nelsoniT pseudospiralisT papuae

*Also includes wild animals.

basin (Morocco, Tunisia, Libya, Israel, the Lebanon,southern Italy, Sardinia, and Spain), the countries of theformer Soviet Union, East Africa (Somalia, Ethiopia, andKenya), South America (Peru, Chile, Argentina, andUruguay), parts of China, Malaysia, Sri Lanka, and India.Prevalence varies widely, ranging from 0.7 to 0.9 per100 000 population in Israel to 1 per 1000 population inthe Turkana Lake area of Kenya. Global mortality isestimated to be 0.2 per 100 000 population.4

In Spain, hydatidosis has been and still is an endemicdisease in many areas (especially in Castile-León, Aragon,Navarra, La Rioja, Madrid, and Castile-La Mancha), withprevalence reaching considerable rates until a few yearsago.25 More recently, however, a decrease has beenobserved in the number of indigenous cases (Table 2),even as the number of imported cases is rising.26

Human schistosomiasis is endemic in 76 countriesworldwide and constitutes one of the most serious publichealth problems facing tropical and subtropical countries.It is estimated that some 200 million people are affected,and that the disease causes between 300 000 and 500 000

deaths annually.27 The infection, which is caused byvarious species of Schistosoma, is more prevalent amongthe young and has a greater impact on their health. As theperson grows older, the parasite load decreases and theindividual’s resistance to reinfection increases.27 Thedistribution of schistosomiasis by species variesdepending on the control strategies being used in the areaand the appearance of new foci of infection.28 In general,S mansoni infection occurs in many African countries,South America (Brazil, Surinam, and Venezuela),numerous Caribbean islands (including Puerto Rico,Saint Lucia, Guadalupe, Martinique, the DominicanRepublic, Antigua, and Montserrat), and in some areas ofthe Middle East. Areas where infection withS haematobium is endemic include a large part ofcontinental Africa, Madagascar and the MauritiusIslands, Saudi Arabia, and the Khuzestan province inIran. The distribution of S japonicum infection is morerestricted. It is found in various parts of China (theregions along the Yangtze river, the lake areas of thecentral region, and the mountainous areas of the

Genus Species Indigenous World Distribution No. of People Affected Cases Worldwide

Echinococcus E granulosus Yes Cosmopolitan Varies greatly, dependingon the affected zone

Schistosoma S mansoni No Africa, South America, the Caribbean, the Middle East 200 millionS haematobium Continental and insular Africa, Saudi Arabia, IranS japonicum China, the Philippines, IndonesiaS intercalatum Central AfricaS mekongi Laos, Cambodia

Paragonimus P westermani No Asia, Africa, South America 22 millionP kellicoti United States of AmericaP africanus AfricaP uterobilateralis AfricaP miyazakii Japan

Ascaris A lumbricoides Doubtful Cosmopolitan 4500 million

Ancylostoma A duodenale No Cosmopolitan

Necator N americanus No Cosmopolitan

Strongyloides S stercoralis Yes CosmopolitanS fuellerborni fuellerboni No AfricaS fuellerborni kelley No Papua-New Guinea

Wuchereria W bancrofti No Africa, India, Southeast Asia, South America 100 million

Brugia B malayi South and Southeast AsiaB timori

Dirofilaria D immitis Yes Cosmopolitan No data available

Toxocara T canis Yes Cosmopolitan No data availableT cati

Trichinella T spiralis Yes Variable depending on the species 11 millionT nativaT britoviT murrelliT nelsoniT pseudospiralisT papuae



TABLE 2Epidemiology of Helminths That Affect the Respiratory System

Szechuan and Yunnan provinces), the Philippines, andIndonesia (the central area of Sulawesi). The distributionof the other 2 forms of Schistosoma infection is verylimited; Schistosoma intercalatum is found in CentralAfrica (principally Gabon, Cameroon, and Zaire, withmore isolated foci in Nigeria, the Central AfricanRepublic, Chad, and Burkina Faso), and Schistosomamekongi is found in Laos and Cambodia.Schistosomiasis is not an indigenous disease in Spainowing, among other factors, to the absence of theappropriate intermediate hosts.29 However, a growingnumber of imported cases are being reported, affectingboth immigrants and travelers. Although the number ofcases reported to the Spanish Microbiologic InformationSystem is low (2 or 3 per year), a review of casespublished and reported at conferences indicates that theincidence of this disease in Spain greatly exceeds this.30-32

Infection by trematodes of the genus Paragonimusaffects some 22 million people worldwide, and isendemic in various parts of Asian, African, and Americancountries.33 The Asian countries most affected are Korea,Japan, Taiwan, central China, and the Philippines.However, the disease has also been reported in Vietnam,Sri Lanka, Indonesia, Malaysia, Laos, and Thailand. InAfrica, it is found in the central and western part of thecontinent, mainly Cameroon, Nigeria, Guinea, Gambia,and Liberia. Cases have been reported in many SouthAmerican countries, especially in Ecuador, Peru,Colombia, Venezuela, and parts of Brazil. The mostpredominant trematode species worldwide isP westermani, although other species are founddepending on the geographical zone (Paragonimuskellicotti in the United States of America,34

Paragonimus africanus and Paragonimus uterobilateralisin Africa,35 and Paragonimus miyazakii in Japan).36

Because of the characteristics of this parasite’s life cycle,most fluke infections are caused by the consumption ofraw or undercooked crustaceans, although they can alsoresult from the consumption of meat from paratenic hosts(pigs, bears, and rats). An interesting development is thepossibility of cases of infection occurring in Westerncountries caused by the consumption of crustaceanspickled in wine or vinegar exported from endemic areas.No indigenous cases of paragonimiasis have beenreported in Spain, and imported cases are rare.37

Diseases caused by geohelminths are the mostcommon parasitic disorders in the world; it is estimatedthat approximately 4500 million people are affected.38

The 3 types of geohelminths that can affect the respiratorystructures are A lumbricoides, hookworm, and Strongyloidesspecies. While infection with A lumbricoides iscosmopolitan, prevalence is higher in developing countrieslocated in tropical and subtropical areas.24 In any case, theprevalence of this infection varies greatly depending onage (predominant in children) and the different regions ofthe countries. In Spain, very few cases (between 10 and20 annually) were reported to the MicrobiologicInformation System until 1999, but the number ofreported cases rose considerably in subsequent years,

probably as a result of immigration.40 No conclusive dataare available on the current presence of indigenous casesin Spain, but in any case they would be rare.41,42

Hookworm infections caused by A duodenale andN americanus are the most prevalent helminthic diseasesworldwide.19 Distribution is cosmopolitan, with thehighest rates occurring in Asia (particularly China) andsub-Saharan Africa. The distribution of N americanus ismore cosmopolitan, while that of A duodenale is restrictedto more specific areas. Unlike ascariasis, hookworminfection predominantly affects adults. Practically the onlycases reported in Spain have been imported.39,43 Infectionwith nematodes of the genus Strongyloides is prevalent inlarge areas of the tropical regions of Asia, Africa, andAmerica, with rates decreasing as the distance from thetropics increases. The 2 main species that infest humansare S stercoralis and S fuelleborni. It is estimated thatbetween 80 and 100 million people living in the temperatezones of the planet are infected with S stercoralis,44 whileinfection with S fuelleborni is found only in Papua NewGuinea and parts of Africa.45 In Spain, cases arecommonly reported of indigenous strongyloidiasis(especially in the Autonomous Community ofValencia),20,46-48 and of imported forms.39,49

There are 2 types of filarial infection that can damagethe respiratory system, lymphatic filariasis anddirofilariasis. Lymphatic filariasis is caused by 3 species(W bancrofti, B timori, and B malayi), and each one has adifferent geographical distribution. W bancrofti infectionhas been reported in approximately 80 countries.Approximately one third of the cases reported have beenin Africa, another third in India, and the balance in SouthAsia, the Pacific rim, and parts of Central and SouthAmerica. The countries with the highest prevalence ratesare India, Nigeria, Bangladesh, Indonesia, theDemocratic Republic of the Congo, the Philippines, andMadagascar.50 Infection with Brugia species is limited toSouth and Southeast Asia, in particular China, India,Indonesia, Malaysia, Timor, Sri Lanka, Thailand, andVietnam. Worldwide, lymphatic filariasis affects some120 million people.38 In Spain, all reported cases oflymphatic filariasis have been imported.51 Infection withD immitis is cosmopolitan. This parasite affects mainlydogs and cats in areas with a warm and temperateclimate, although it is spreading progressively to otherregions of the planet. This infection usually affectscanids, particularly dogs, and it is only rarely diagnosedin humans.14 The intermediate hosts are approximately70 species of mosquito belonging to various genera(Culex, Aedes, Anopheles, and Mansonia). In Spain,pulmonary dirofilariasis has been described as anindigenous disease in the province of Salamanca,52,53

although the high seroprevalence in dogs in other parts ofthe country, such as the Canary Islands,54 suggests thatthis entity may be underdiagnosed.

Trichinosis is a disease of worldwide distribution,and it is currently estimated that over 11 million peopleare infected.55 Trichinosis usually appears in the form ofoutbreaks owing to the characteristics of the life cycle



of the causative agent. These outbreaks occur in verydiverse areas of the world including Eastern Europe(Russia, Romania, Poland, Bulgaria, former Yugoslavia,and the Baltic republics), the rural areas of Asia(especially China), and some South American countries(Argentina, Uruguay, Chile, and Mexico). The differentspecies of Trichinella occupy different ecologicalniches. The most cosmopolitan species are T spiralisand T pseudospiralis, while the distribution of the otherspecies is more restricted (for example, T nativa—which can survive freezing temperatures—is found insubarctic areas, whereas T nelsoni—which is capable ofsurviving high temperatures—is found in tropicalregions).56 In Spain, trichinosis is mainly an indigenousdisease, and outbreaks have been reported in variousregions.57

It is difficult to establish the prevalence oftoxocariasis in any region or country for the followingreasons: a) the clinical picture is not pathognomonic, b)no direct parasitological diagnosis exists, and c)serologic techniques have a high cross-reactivity rate.Consequently, the data on diagnosis of clinical cases oftoxocariasis (visceral larva migrans) in Spain areanecdotal with respect to both indigenous and importedcases. However, the high seroprevalence in humans invarious regions of Spain (32.8% in children in Galicia,58

3.4% in the general population in the Canary Islands,59

14.1% in people with eosinophilia in Barcelona,60 8.5%in children living in the urban areas of Salamanca,61 and1% in children in Madrid62) suggests the existence ofasymptomatic forms or underdiagnosis of clinicalforms.

Disease Mechanisms and Clinical Manifestations

The helminths described above cause clinical signsand symptoms affecting the respiratory system by wayof 2 main mechanisms: a) mechanical lesions caused bythe presence of the parasite or by obstruction ofvascular or bronchial structures; and b) immunological

response to the parasite or one of its component parts.The clinical signs and symptoms are sometimes scant,in which case abnormalities in the results of basicexploratory tests (for example, a chest radiographand/or a complete blood count) are what reveal thepresence of the helminthiasis.

Table 3 lists the main clinical and biological patternsof pulmonary involvement and the helminths that causethem.

Pulmonary Mass or Nodule

The 2 types of helminthiasis that give rise to thispattern are hydatid disease (1 or more pulmonarymasses) and dirofilariasis (pulmonary nodules).

Hydatid disease is the most common form ofpulmonary helminthiasis. The clinical and biologicalmanifestations of this disease vary according to thenumber and state of the cysts present. The incubationperiod between contagion and the appearance of signsand symptoms varies widely, ranging from months to,more frequently, years. Although cases have beenreported in patients of all ages from 1 to 75 years, themost common age range in the Mediterranean area isbetween 20 and 40 years. The prevalence is similar inmales and females.4,17,63 In general, pulmonaryhydatidosis is more common in children than the purehepatic form of the disease is, an observation that hasbeen attributed to the greater relative compressibility ofthe lung parenchyma.64 Associated liver damage is lesscommon than would appear logical from the pathogenicstandpoint (20%-40%) and may depend on the strain ofE granulosus responsible for the infection.65 Overall, itis estimated that 70% to 80% of cases have solitary cystsand that multiple cysts are present in 20% to 30% ofcases.64,66 Cysts are usually located in the lower lobes,especially in the lower region, and are evenly distributedin both lungs; size ranges from 1 to 20 centimeters.64,66

Clinical signs and symptoms depend on whether the cystis intact or has ruptured and on the complications that



TABLE 3Main Clinical Syndromes Associated With the Forms of Helminthiasis That Affect the Respiratory System

Clinical/Biological Pattern Subtypes Clinical Syndromes Causative Agents

Pulmonary mass or nodule Echinococcus granulosus. Dirofilaria immitis

Lung infiltrations Without nonpulmonary involvement Löffler syndrome Ascaris species. Ancylostoma duodenale. Necator americanus

Tropical pulmonary eosinophilia Wuchereria bancrofti. Brugia malayi. Brugia timori

With nonpulmonary involvement Katayama syndrome Schistosoma speciesVisceral larva migrans Toxocara speciesHyperinfection syndrome Strongyloides species

Miliary pattern/pulmonary hypertension Schistosoma species

Pleural effusion Paragonimus species

Muscular involvement Trichinella species

have been caused by the rupture.67 Therefore, patientswith uncomplicated pulmonary hydatid disease areusually asymptomatic; the most typical sign of aruptured cyst is expectoration of hydatid material, whilein complicated forms of the disease (with, for example,secondary bacterial infection or rupture into the pleuralcavity) the patient presents multiple signs andsymptoms.67 In large case series, the features mostcommonly reported were cough (62%), chest pain(56%), expectoration (42%), and fever (32%).17 Up to10% of cases may develop systemic anaphylaxis duringrupture.17 Depending on the state of the cyst, imagingstudies contribute a rich semiology, which has beenreviewed in depth by Pedrosa et al64 and Ramos et al.67

Pulmonary dirofilariasis in humans is usuallydetected by way of radiographic abnormalities inasymptomatic patients or by the presence of nonspecificrespiratory symptoms.13 The most common clinical signis the presence of pulmonary nodules (persistent ortransient) or granulomas.13,52,53

Pulmonary Infiltrates

Pulmonary helminth infection is also detected whenthe patient develops respiratory symptoms (cough,expectoration, dyspnea, and occasionally hemoptysis orchest pain) in association with alveolar infiltrates onplain chest radiography. Concurrent nonpulmonaryinvolvement can help to guide the diagnosis.

Without nonpulmonary involvement. The 2 typicalclinical pictures are Löffler syndrome and tropicalpulmonary eosinophilia. Löffler syndrome is one of themost confusing denominations in medicine. In additionto the linguistic problems it poses,68 the term is used in2 different ways in the medical literature. It is used torefer to both transient eosinophilic pulmonaryinfiltrates69 and to endocarditis/myocarditis in a patientwith eosinophilia.70 In the first case, the originaldescription of Löffler syndrome referred to the transitof a helminth (probably Ascaris species) through thelung,71 but the term was later applied to cases ofpulmonary involvement and eosinophilia associatedwith parasitosis without transbronchial transit72 andeven to transient pulmonary infiltrates caused by drugreactions.73 In the strictest sense, the syndrome ischaracterized by the appearance of pulmonaryinfiltrates and peripheral blood eosinophilia secondaryto transbronchial migration of Ascaris species.74

Although classic texts often assert that hookworm, andeven Strongyloides species, can be associated withLöffler syndrome, well documented cases are rare.

Tropical pulmonary eosinophilia, however, is a welldefined syndrome.75 Its pathogenesis is a hypersensitivityreaction to antigens of lymphatic filariae (Wuchereriaspecies and Brugia species). Clinically, this syndrome isfound mainly among males whose average age fallssomewhere between 20 and 30 years, and importantracial differences exist—the highest prevalence is found

in India. The clinical picture is usually characterized bysevere asthma that does not respond well to conventionaltreatment. No abnormalities are found in the chestradiograph of 20% of patients; in the other 80%, the mostcommon finding is reticulonodular infiltrates locatedmainly in the intermediate and lower lung fields.

With nonpulmonary involvement. When there isnonpulmonary involvement, the main candidate diagnosesare Katayama syndrome, toxocariasis (visceral larvamigrans), and Strongyloides hyperinfection syndrome.

Since Katayama syndrome is characteristic of acuteschistosomiasis it is found more often in travelers thanin immigrants.8,76 When taking a clinical history it isstandard practice to check whether the patient has beenin contact with potentially infected fresh water 15 daysto 3 months before the appearance of signs andsymptoms. In the complete form of the syndrome,patients present with fever, headache, generalizedmuscular pain, pain in the right hypochondrium, andnonspecific respiratory symptoms (cough, dyspnea).Respiratory symptoms are more common in S mansoniinfection than in disease caused by S haematobium.Physical examination often reveals painfulhepatomegaly and occasionally splenomegaly. The mostcommon abnormal findings are eosinophilia (almostalways present) and abnormalities in the chestradiograph, primarily micronodular infiltrates, alveolarconsolidation, and bronchial wall thickening.77 Thisclinical picture is produced by a hypersensitivityreaction to the helminth. Since this reaction occursduring a stage in the parasite’s life cycle beforeoviposition, direct parasitological studies (examinationof stools and urine for eggs) are negative at this time.

Visceral toxocariasis (visceral larva migrans) is achildhood disease found primarily in children who eatdirt and/or bite their nails.15,78 The typical clinicalsigns are hepatic (painful hepatomegaly) andpulmonary (bronchospasm). Other manifestations thatmay occur include cutaneous symptoms (pruritus andurticaria), articular lesions (arthritis), myocarditis,glomerulonephritis, and neurological abnormalities(for example, epileptic seizures). The presence ofelevated transaminase and immunoglobulin levels andeosinophilia is a very typical finding in basic bloodanalysis.

Strongyloides species infection in immunocompetentpatients does not usually give rise to respiratorysymptoms, although the presence of asthma has beenattributed to this helminth in some cases. However, thesituation is different in the case of disseminatedstrongyloidiasis, a condition usually caused byhyperinfection.79 Although cases of disseminatedstrongyloidiasis in immunocompetent individuals havebeen reported, this entity is usually associated with 2risk factors: corticosteroid use and human T-celllymphotrophic virus type 1 infection.79,80 In thesecircumstances, the rhabditiform larvae molt and becomefilariform larvae, which then enter the bloodstream. The



pulmonary signs and symptoms are very varied andcorrespond to 2 lesional patterns found in isolation or inassociation: a) bacterial infection (caused by bacteriatransported from the intestinal tract); and b) diffusealveolar hemorrhage.79-83 The clinical picture variesconsiderably, ranging from presentations with very fewsymptoms to more severe disease characterized bydyspnea, variable cough, hemoptysis, and precordialpressure. Digestive symptoms are also very common(abdominal pain, nausea, vomiting, diarrhea, andconstipation). Chest radiography often reveals bilateralor focal interstitial pulmonary infiltrates. Unlike theother entities discussed, disseminated strongyloidiasis isnot associated with eosinophilia, and this makes it moredifficult for the clinician to reach a tentative diagnosis.Filariform or rhabditiform larvae and even parasite eggscan be detected in sputum and other respiratory samples.

Miliary Pattern and Pulmonary Hypertension

Chronic schistosomiasis is characterized by a miliarypattern found in association with pulmonaryhypertension (and even findings indicative of corpulmonale).77,84 This form of the disease corresponds toa granulomatous inflammatory response secondary toschistosome egg embolization; the hypertension issecondary to the granulomatous lesions. The clinicalsigns and symptoms—which are caused by thepulmonary hypertension—include dyspnea and dullchest pain, and in some cases findings indicative ofright heart failure. The most characteristic finding on



TABLE 4Direct Diagnosis of the Helminthic Diseases That Affect

the Respiratory System

Genus Species Direct Diagnosis

Echinococcus E granulosus Visual identification of parasites in expectorated material*

Schistosoma Visual identification of eggs in feces and urine

Paragonimus Visual identification of eggs in sputum or feces

Ascaris A lumbricoides Visual identification of eggs in feces

Ancylostoma A duodenale Visual identification of eggs in feces

Necator N americanus Visual identification of eggs in feces

Strongyloides Visual identification of larvae in feces, sputum or bronchoalveolar lavage (direct examination, Baermann technique, Harada-Mori technique, and culture in agar)

Wuchereria W bancrofti Detection of microfilariae in blood (Knott)

Brugia B malayi Immunochromatographic B timori test (Wuchereria species)

Dirofilaria D immitis None available

Toxocara None available

Trichinella Muscle biopsy

*Rare in practice (only undertaken when cystic material is expectorated)

TABLE 5Treatment of the Helminthic Diseases that Affect the Respiratory System

Genus Species Treatment References

Echinococcus E granulosus Surgery and/or antiparasitic drugs (albendazole ± praziquantel) 4, 66, 67, 94, 95, 96

Schistosoma Katayama fever: praziquantel, 20 mg/kg every 12 h for 3 consecutive days 27, 97+ corticosteroids

Chronic forms 84Praziquantel, 20 mg/kg every 12 hours (1 day)Symptomatic treatment

Paragonimus Praziquantel, 75 mg/kg/day for 3 consecutive days 85Pleural drainage

Ascaris A lumbricoides Albendazole, 400 mg as a single dose 12

Ancylostoma A duodenale

Necator N americanus

Strongyloides Ivermectin 11

Wuchereria W bancrofti Tropical pulmonary eosinophilia 75Classic treatment: diethylcarbamazine, 6 mg/kg/day for 21 days

Brugia B malayi Alternative options: ivermectin + corticosteroidsB timori

Dirofilaria D immitis Unnecessary 52, 53

Toxocara Albendazole, 400 mg/12 h for 5 consecutive days 15

Trichinella Albendazole, 400 mg/day for 3 days followed by albendazole, 98400 mg/12 h for 15 days + corticosteroids

chest radiography is a miliary pattern (similar to that oftuberculosis) and the typical images associated withpulmonary hypertension.

Pleural Effusion

While pleural effusion may appear in several of theforms of helminthiasis mentioned above, thisrespiratory manifestation is particularly relevant in thecase of paragonimiasis.85 It is found in between 40%and 70% of patients and is associated with damage tothe underlying lung parenchyma in the form of cysticlesions or nodules. While approximately 20% ofpatients in whom respiratory disease is detected byimaging studies are asymptomatic, the others presentsome symptom, such as cough or chest pain. Anassociation with peripheral eosinophilia is very oftenfound, particularly in cases with pleural involvement.

Muscular Involvement

Infection with different species of Trichinellaprimarily affects striated muscle tissue (skeletal orcardiac).86 Consequently, pulmonary involvement intrichinosis is a result of involvement of the respiratorymusculature and in particular of the diaphragm, themuscle most often affected.87 More rarely, pulmonarysymptoms may be due to the development ofmyocarditis and heart failure.87

Diagnosis

Diagnosis of pulmonary helminthiasis dependsinitially on clinical suspicion based on the patternsdiscussed above. Except in the cases of pulmonarydirofilariasis and Strongyloides hyperinfectionsyndrome, peripheral blood eosinophilia is a commonfinding that can alert the clinician to suspect a possiblediagnosis of helminthic disease. Once a tentativediagnosis has been reached, direct methods (detectionof the parasite itself, or of specific proteins or geneticmaterial) and indirect techniques (serology) are used tofacilitate the final diagnosis.88-93 Table 4 summarizes theprincipal direct diagnostic techniques. Althoughcommercial diagnostic procedures are available, we feelit is pertinent to indicate that these techniques can yieldfalse results (both positive and negative), and that suchfailure gives rise to significant error in clinical practice(T. Gárate, personal communication).

Treatment

The treatment of helminthiasis affecting therespiratory system is principally pharmacological,with surgery being reserved for patients withhydatidosis.4,11,12,15,27,52,53,66,67,84,85,94-98 The drugs mostcommonly used are albendazole, ivermectin,praziquantel, and diethylcarbamazine—the last 3 ofwhich are only available from suppliers outside Spain.

The treatment of pulmonary hydatidosis is based onsurgery and/or pharmacotherapy (albendazole and/orpraziquantel).4,66 The PAIR strategy (involvingpuncture, aspiration, injection, and re-aspiration) usedin other areas of the body is not useful in this site.Surgery is the first-line treatment in the presence oflarge cysts, superficially located cysts, vital organinvolvement, local complications, or a mass effect ofcysts. For a comprehensive review of specific surgicaltechniques see Ramos et al.67 Irrespective of thetechnique used, 2 considerations are important: a) iffeasible, preoperative treatment (with albendazole aloneor in combination with praziquantel) for 1 month willreduce the viability of the parasite;94,95 and b) it isessential to avoid the dissemination of protoscolicesduring the intervention. However, the utility of theintraoperative use of protoscolicidal agents (ethanol,hypertonic saline solution, and cetrimide) has not beenclearly established. In addition to its preoperativeutility, treatment with antiparasitic drugs is anappropriate option in cases that do not fulfill the above-mentioned indications for surgery. The most effectiveagent is albendazole used alone or in combination withpraziquantel, the effect of which is indirect as it servesto increase the concentrations of albendazole. While 3-and 6-month cycles of albendazole were prescribedtraditionally, with 15-day intervals between cycles,recent studies indicate that continuous treatment ismore effective.95

Table 5 shows the most useful therapeutic regimesfor the other parasites discussed.

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